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  2. Repetitive restraint stress changes spleen immune cell subsets through glucocorticoid receptor or β-adrenergic receptor in a stage dependent manner

Repetitive restraint stress changes spleen immune cell subsets through glucocorticoid receptor or β-adrenergic receptor in a stage dependent manner

  • Biochem Biophys Res Commun. 2018 Jan 1;495(1):1108-1114. doi: 10.1016/j.bbrc.2017.11.148.
Yu Li 1 Wei Jiang 1 Zhen-Zhen Li 2 Chen Zhang 2 Chen Huang 3 Jun Yang 4 Guang-Yao Kong 5 Zong-Fang Li 6
Affiliations

Affiliations

  • 1 National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, Xi'an, China; Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • 2 National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • 3 National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Key Laboratory of Environment and Disease-Related Gene, Ministry of Education, Xi'an Jiaotong University, Xi'an, China.
  • 4 National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Department of Pathology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. Electronic address: yangjundr@163.com.
  • 5 National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. Electronic address: konggy@xjtu.edu.cn.
  • 6 National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, Xi'an, China; Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. Electronic address: lzf2568@mail.xjtu.edu.cn.
Abstract

Immune system is sensitive to stress. Spleen is the largest peripheral immune organ innervated with sympathetic nerves and controlled by adrenomedullary system in the body. However, the alterations and mechanism of spleen immune cell subsets caused by repetitive restraint stress (RRS) is poorly understood. In this study, we found that RRS reduced spleen index in mice, and induced an expansion of white pulp and involution of the red pulp. Meanwhile, the percentage of CD3+CD8+ T lymphocytes, CD11b+F4/80+ macrophages, CD11b+Ly-6G-Ly-6Chi monocytic myeloid derived suppressor cells (mMDSCs) and CD11b+Ly-6G+Ly-6Cint granulocytic myeloid derived suppressor cells (gMDSCs) in spleen were significantly changed by RRS. Mechanistically, we found that the expression of norepinephrine (NE) and β-adrenergic receptor (β-AR) in spleen were up-regulated after 21 days of RRS, but not 7 days. The expression of corticosterone (CORT) and Glucocorticoid Receptor (GR) in spleen were up-regulated after 7 days of RRS but were lower after 21 days of RRS, even though they were still higher than that in mice without stress. By treating the stressed mice with RU486 (antagonist of GR) or propranolol (antagonist of β-AR), we demonstrated that GR was responsible for the changes of spleen induced by 7 days of RRS and β-AR was for 21 days of RRS. Our data suggest that RRS changes spleen immune cell subsets through GR or β-AR in a stage dependent manner.

Keywords

Glucocorticoid receptor; Propranolol; RU486; Repetitive restraint stress; Spleen; β-adrenergic receptor.

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